Abstract Mechanisms of mindfulness for smoking cessation: optimizing quantity and quality. Cigarette smoking is the leading preventable cause of death in the U.S., costing more than $193 billion in health care costs and lost productivity annually. There is a growing body of evidence that mindfulness training (MT) is effective for addictions, including alcohol and nicotine use disorders. Early results suggest that on a psychological level, MT may target the link between craving and smoking. In other words, mindfulness may help individuals ?ride out? cravings instead of getting caught up in them - without smoking. However, the neurobiological mechanisms underlying the efficacy of MT for addictions are unknown. We have developed a mobile app-based MT program for smoking cessation, which has shown preliminary efficacy in smoking cessation (Craving to Quit, C2Q). Mobile trainings such as this are ideal for providing standardized delivery of treatment, which helps minimize variability when studying underlying neurobiological mechanisms. Given their electronic platforms, these tools can also be more easily monitored for adherence and adapted for refinement. We have also developed a real-time EEG neurofeedback device that can provide source-estimated feedback from specific brain regions. This is now being tested in clinical trails to examine if it can augment mindfulness acquisition in individuals who are taking Mindfulness-Based Stress Reduction (MBSR). However, this technology has not been tested in clinical populations or for specific conditions or disorders. Bringing all of these elements together, we now have an opportunity to (1) determine the mechanism of mindfulness in cue-induced smoking; (2) test strategies to enhance engagement in mobile MT; and (3) determine if neurofeedback can strengthen identified mechanisms of MT. In the proposed study, Aim 1 will determine if mindfulness training alters neural correlates of cue reactivity in smokers. To achieve this, smokers will be randomized to receive MT (C2Q) vs. an active control (experience sampling). Cue-induced PCC activity will be measured pre- and post- training. Aims 2 and 3 will optimize treatment engagement and quality of mindfulness skills. This proposed phased research approach will be the first to uncover the neurobiological mechanisms of mindfulness for smoking (and potentially addiction more broadly). It will utilize these results to refine both quantity and quality of mobile MT while providing preliminary evidence that the modulated mechanisms of mindfulness are associated with clinical benefits, including smoking cessation.